Research Models

ALS Mouse Models

Dozens of rodents have been generated that model various aspects of ALS, like motor impairment or degeneration of motor neurons. No model recapitulates the human disease perfectly. By organizing information related to the phenotypic characterization of selected ALS models, this resource conveys what is known about each one and facilitates comparison between models. The curation of ALS models was supported in part by a grant from the NINDS.

RNA foci throughout the nervous system starting at 3 months of age. Foci comprised of RNA transcripts in both the sense and antisense directions. Age-associated formation of dipeptide aggregates, e.g., poly-GP.

No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.

Not observed.

Not observed.

No abnormalities in grip strength, Rotarod performance, or open-field testing at a young age (3 months) or advanced age (18 months), compared with non-Tg controls.

No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.

Compared with mice expressing 2-repeats, the 66-repeat mice had 17 percent fewer neurons in the cortex at 6 months of age and 11 percent fewer Purkinje cells in the cerebellum. At this age neurons in the hippocampus and thalamus were not affected.

At 6 months, neuronal loss in the spinal cord was not detected.

By 6 months, inclusions of C9RAN dipeptides were present in neurons of the cortex and hippocampus, and to a lesser extent in the cerebellum and spinal cord. Inclusions contained polyGA, polyGP, and polyGR dipeptides and were largely ubiquitin-positive.

Astrogliosis in the cortex by 6 months.

No data.

No data.

At 6 months, 66-repeat mice perform as well as 2-repeat mice on the Rotarod on the first day of testing. However, they fail to improve during subsequent trials, suggesting impairments in coordination and/or motor learning.

At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.

Neuronal numbers comparable to wild-type at 15 weeks, but about 20 percent loss of upper motor neurons by 29 weeks. Neurons in layer V of the motor cortex appeared selectively vulnerable.

Neuronal numbers comparable to wild-type at 6 weeks, but loss occurred by 15 weeks. The neuronal loss then stabilized; it was not more severe at 52 weeks of age.

Not observed.

Gliosis, of both astrocytes and microglia, was evident in the spinal cord by 15 weeks. It was further elevated at 52 weeks.

Denervation of a hindlimb muscle, the extensor digitorum longus, was detected by 52 weeks of age, and a decreased number of motor units in the EDL muscle.

Muscle atrophy was not reported, although changes to the muscle composition and histochemistry were observed.

Both male and female mice develop a variety of progressive motor symptoms. Grip strength was reduced at 6 weeks of age. Tremors developed by about 5 months of age. Rotarod performance was impaired, at 23 weeks in females and 67 weeks in males.

Homozygous mice, both male and female, showed reduced body weight by 4 weeks of age in contrast to wild-type littermates. Loss of excessive body weight was the primary factor leading to euthanasia.

Males reach end-stage sooner than females (495 ± 22 versus 588 ± 24 days). Animals were sacrificed when weight loss exceeded 20 percent of maximum weight, in accordance with animal-use guidelines. This is likely explained by the development of hepatocellular carcinomas due to SOD1 loss of function.

In the brain, overt neuronal loss was absent at end stage (~11 weeks).

By end stage (~11 weeks), homozygous mice had lost about 60 percent of α-motor neurons in the anterior horn of the lumbar spinal cord.

By end stage, cytoplasmic FUS inclusions, described as “granular” and “globular,” develop in the spinal cord of homozygous mice. Ubiquitin-positive inclusions also develop, but do not co-localize with FUS inclusions. Neurons in the brain also develop “granular” and “skein-like” FUS inclusions.

By end stage (~11 weeks), homozygous mice had microgliosis and astrogliosis in the anterior horn of the spinal cord and in the white matter of the dorsal columns. Reactive gliosis was absent in the brain, despite cytoplasmic inclusions of FUS in some neurons.

Severe neuronal degeneration in the dentate gyrus and deep layers of the neocortex. Other regions, such as the hippocampal CA1 subfield and olfactory bulb, were relatively resistant to neurodegeneration. Approximately 50 percent of dentate gyrus neurons were lost one month after the transgene was activated.

Not observed.

High levels of cytosolic TDP-43 but only very rare aggregates (observed in less than 1 percent of cortical neurons and even rarer in other brain regions, such as the hippocampus and striatum).

Severe astrogliosis and microgliosis in areas affected by neurodegeneration, including cortical and hippocampal regions, as well as the corticospinal tract.

Unknown.

Not observed.

Spastic motor impairment indicated by an abnormal clasping response as early as one week after transgene induction. A variety of motor deficits develop by one month after transgene induction, including impaired coordination on the Rotarod and decreased grip strength.

Decreased cortical thickness indicative of neuronal degeneration beginning at four weeks off dox. By end stage, rNLS8 mice had significantly smaller brains than non-Tg littermates.

rNLS8 lost motor neurons in the lumbar spinal cord by six weeks off dox.

Cytoplasmic inclusions of TDP-43 occur as early as one week off dox in neurons in the brain. Inclusions accumulate over time and are present in many brain regions, including the motor cortex. TDP-43 inclusions are relatively rare in the spinal cord. Ubiquitin-positive inclusions are also seen.

Astrogliosis develops in many brain regions, including layer V of the motor cortex.

Denervation of the hindlimb muscle tibialis anterior was detectable by four weeks off dox, that is, two weeks prior to detectable loss of lower motor neurons.

rNLS8 mice develop a variety of motor impairments, starting with a deficit in hindlimb clasping and a fine tremor in the forelimb and/or hindlimb. They also develop progressive loss of grip strength (as measured by the wire-hang test) and a progressive decline in coordinated movement and balance (as measured by the accelerating Rotarod).

Body mass peaked at approximately 7 weeks of age (i.e., two weeks off dox) and then progressively dropped. Excessive loss of body weight (>30% decrease from peak weight) often defined end-stage.

rNLS8 mice die prematurely. They reach end-stage 8-18 weeks off dox, with a median survival of 10.3 weeks off dox.

Despite high levels of cytoplasmic FUS, neuronal inclusions were not observed.

No data.

A number of abnormalities were detected in the hindlimb musculature by electromyography (EMG). These phenotypes were detectable by 8-12 months of age and included fibrillation potentials, muscle denervation, and a reduction in the number of motor units.

No data.

Not observed.

No data.

Hemizygous mice sporadically developed intestinal swelling leading to premature death (mean survival 118 days). Homozygous mice were more severely affected (50 percent of the original cohort died around 59 days of age).

Upper motor neuron loss was not observed, although vacuolization occurred in brainstem neurons.

Motor neurons in the spinal cord and brainstem degenerated with overt neuronal loss in the ventral horn in some regions of the spinal cord by 19 weeks. The degenerative process involved extensive vacuolization.

Not observed.

Astrogliosis occurs in the spinal cord by 11 weeks of age, becoming more severe with age.

Although outright upper motor neuron loss is absent or rare, degenerative signs (e.g., swollen neurites, Gallyas-positive aggregates, vacuoles, and neuritic spheroids) have been shown in motor regions of the cerebral cortex by five months of age.

Up to 50% loss of motor neurons in the cervical and lumbar segments of the spinal cord at end stage.

Inclusions accumulate in spinal motor neurons starting around 82 days of age. Inclusions generally take the form of spheroids or Lewy-body-like inclusions and commonly include a variety of neuronal intermediate filament proteins. TDP-43-positive inclusions are not present.

Gliosis, including the proliferation of reactive microglia and astrocytes, develops in parallel with motor neuron degeneration in the spinal cord.

These mice lose corticospinal tract axons, but outright loss of cortical neurons has not been reported in the model. When crossed with a Thy-1YFP model to label layer 5 pyramidal neurons, mice expressing TDP-43 (A315T) had fewer neurons at 15 weeks of age than YFP littermate controls (Zhang et al., 2016).

Most studies reported no lower motor neuron loss. One study observed 20% loss of large ventral horn neurons, possibly dependent on diet and how long the mice live in an individual colony.

Ubiquitinated inclusions in the cytoplasm of spinal motor neurons and cortical layer V neurons. No evidence for cytoplasmic TDP-43 inclusions.

Reports of astrocytosis in cortical layer 5 and in the spinal cord, as well as microgliosis in the spinal cord.

Denervation of neuromuscular junctions at end stage (~11% on normal diet; ~20% loss on a gel diet).

Atrophy of gastrocnemius muscle (gel diet).

Deficits have been reported in nonspecific measures of strength and coordination such as the Rotarod (males and females) and hanging-wire test (males). A severely impaired gait (“swimming gait”) was observed in mice fed a gel diet.

Survival is limited by severe gastrointestinal dysfunction and can be prolonged with a gel diet. Lifespan varies, but in general on a standard diet males live about 3 months and females about 6 months.

Cytoplasmic accumulation of TDP-43 was observed by 10 months of age in the spinal cord. Furthermore, cytoplasmic aggregates were observed and often co-localized with ubiquitin. These inclusions are not detected at three months of age.

Progressive gliosis of both astrocytes and microglia, starting at a young age (by 3 months) in the brain and spinal cord.

Unknown.

Unknown.

At 38 weeks of age, mice develop impairments on the accelerating Rotarod relative to non-Tg littermates.

Ubiquitin-positive cytoplasmic inclusions in neurons of the ventral horn and brainstem. Cytoplasmic aggregates of TDP-43 are largely absent, although rare phospho-TDP-43 inclusions were observed, especially at end-stage.

Mice exhibiting muscle weakness had astrocytosis in the ventral horn of the spinal cord.

Unknown.

Atrophy of muscle fibers in the quadriceps muscle of weak mice observed by day 44.

Progressive motor impairment, characterized by weakness, a decline in grip strength, and reduction in stride length. Weakness was usually more pronounced in the hindlimbs.

Progressive weight loss.

Line 23 mice survived about 2.5 months, mean survival 75 days. It was not reported whether this survival analysis includes males, females or both. Colony at Jackson Labs has longer mean survival.

Cytoplasmic accumulation of TDP-43 was observed by 10 months in the spinal cord. Cytoplasmic aggregates occurred and often co-localized with ubiquitin. These inclusions are not detected at 3 months of age.

Progressive gliosis of both astrocytes and microglia, starting at a young age (by 3 months) in the brain and spinal cord.

In 10-month-old mice, approximately 10% of NMJs in the gastrocnemius muscle were denervated, with another 20% partially denervated.

Unknown.

Performance on the Rotarod was comparable to non-Tg littermates until 36 weeks of age, and became progressively worse with age.

Severe neuronal loss in all CA regions of the hippocampus of homozygous mice. Neuronal loss was also observed in layer V cortical neurons and thalamic neurons.

Neuronal loss was observed in the spinal cords of homozygous mice.

Some homozygous mice developed cytoplasmic inclusions in layer V cortical neurons. These were often, but not always, ubiquitin–positive. They were not universally observed, even in end-stage mice.

Elevated astrogliosis and microgliosis compared with non-Tg controls, especially in the motor cortex and spinal cord. Gliosis in the hippocampus was seen at end stage.

Unknown.

Unknown.

Motor impairment developed quickly, by 11 days of age in homozygous mice, starting with an abnormal clasping reflex. They also develop a hunched posture, muscle twitches, and reduced mobility. Paralysis developed within days, leading to death. Hemizygotes do not develop motor symptoms until about one year of age, and impairment varied from mouse to mouse.

Early postnatal growth retardation in homozygous mice. By day 17 their average body weight is about half that of non-Tg controls.

Homozygous mice survived an average of just 17 days. In contrast, hemizygous Mt-TAR6 mice lived up to 24 months (average survival ~16.4 months).

In homozygous mice, quantitative loss of neurons occurs in the motor cortex compared with non-Tg littermates. Both superficial and deep cortical layers of the anterior cortex are affected.

By day 18, homozygous mice exhibited about 25 percent loss of motor neurons in the lumbar spinal cord compared with non-Tg littermates.

Homozygous mice developed cytoplasmic inclusions in the brain and spinal cord, many of which were ubiquitin-positive. A minority of inclusions co-labeled with TDP-43. Ultrastructural analysis revealed ubiquitin–negative cytoplasmic inclusions in anterior horn neurons to be abnormal accumulations of mitochondria.

Astrogliosis and microgliois especially in cortical layer V of the anterior cortex, including motor and somatosensory cortex, and in the spinal cord.

No data.

No data.

Homozygous mice exhibit an abnormal clasping reflex by postnatal day 14. Other early motor deficits include a shortened stride, a wide stance, and frequent stumbling. By day 18, reduced performance on the Rotarod. Complete paralysis occurs ~10 days after onset.

RNA foci throughout the nervous system starting at 3 months of age. Foci comprised of RNA transcripts in both the sense and antisense directions. Age-associated formation of dipeptide aggregates, e.g., poly-GP.

Absent

No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.

Absent

Not observed.

Absent

Not observed.

Absent

No abnormalities in grip strength, Rotarod performance, or open-field testing at a young age (3 months) or advanced age (18 months), compared with non-Tg controls.

Absent

No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.

Compared with mice expressing 2-repeats, the 66-repeat mice had 17 percent fewer neurons in the cortex at 6 months of age and 11 percent fewer Purkinje cells in the cerebellum. At this age neurons in the hippocampus and thalamus were not affected.

Absent

At 6 months, neuronal loss in the spinal cord was not detected.

Observed

By 6 months, inclusions of C9RAN dipeptides were present in neurons of the cortex and hippocampus, and to a lesser extent in the cerebellum and spinal cord. Inclusions contained polyGA, polyGP, and polyGR dipeptides and were largely ubiquitin-positive.

Observed

Astrogliosis in the cortex by 6 months.

No Data

No data.

No Data

No data.

Observed

At 6 months, 66-repeat mice perform as well as 2-repeat mice on the Rotarod on the first day of testing. However, they fail to improve during subsequent trials, suggesting impairments in coordination and/or motor learning.

Observed

At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.

Neuronal numbers comparable to wild-type at 15 weeks, but about 20 percent loss of upper motor neurons by 29 weeks. Neurons in layer V of the motor cortex appeared selectively vulnerable.

Observed

Neuronal numbers comparable to wild-type at 6 weeks, but loss occurred by 15 weeks. The neuronal loss then stabilized; it was not more severe at 52 weeks of age.

Absent

Not observed.

Observed

Gliosis, of both astrocytes and microglia, was evident in the spinal cord by 15 weeks. It was further elevated at 52 weeks.

Observed

Denervation of a hindlimb muscle, the extensor digitorum longus, was detected by 52 weeks of age, and a decreased number of motor units in the EDL muscle.

No Data

Muscle atrophy was not reported, although changes to the muscle composition and histochemistry were observed.

Observed

Both male and female mice develop a variety of progressive motor symptoms. Grip strength was reduced at 6 weeks of age. Tremors developed by about 5 months of age. Rotarod performance was impaired, at 23 weeks in females and 67 weeks in males.

Observed

Homozygous mice, both male and female, showed reduced body weight by 4 weeks of age in contrast to wild-type littermates. Loss of excessive body weight was the primary factor leading to euthanasia.

Observed

Males reach end-stage sooner than females (495 ± 22 versus 588 ± 24 days). Animals were sacrificed when weight loss exceeded 20 percent of maximum weight, in accordance with animal-use guidelines. This is likely explained by the development of hepatocellular carcinomas due to SOD1 loss of function.

In the brain, overt neuronal loss was absent at end stage (~11 weeks).

Observed

By end stage (~11 weeks), homozygous mice had lost about 60 percent of α-motor neurons in the anterior horn of the lumbar spinal cord.

Observed

By end stage, cytoplasmic FUS inclusions, described as “granular” and “globular,” develop in the spinal cord of homozygous mice. Ubiquitin-positive inclusions also develop, but do not co-localize with FUS inclusions. Neurons in the brain also develop “granular” and “skein-like” FUS inclusions.

Observed

By end stage (~11 weeks), homozygous mice had microgliosis and astrogliosis in the anterior horn of the spinal cord and in the white matter of the dorsal columns. Reactive gliosis was absent in the brain, despite cytoplasmic inclusions of FUS in some neurons.

Severe neuronal degeneration in the dentate gyrus and deep layers of the neocortex. Other regions, such as the hippocampal CA1 subfield and olfactory bulb, were relatively resistant to neurodegeneration. Approximately 50 percent of dentate gyrus neurons were lost one month after the transgene was activated.

Absent

Not observed.

Absent

High levels of cytosolic TDP-43 but only very rare aggregates (observed in less than 1 percent of cortical neurons and even rarer in other brain regions, such as the hippocampus and striatum).

Observed

Severe astrogliosis and microgliosis in areas affected by neurodegeneration, including cortical and hippocampal regions, as well as the corticospinal tract.

No Data

Unknown.

Absent

Not observed.

Observed

Spastic motor impairment indicated by an abnormal clasping response as early as one week after transgene induction. A variety of motor deficits develop by one month after transgene induction, including impaired coordination on the Rotarod and decreased grip strength.

Decreased cortical thickness indicative of neuronal degeneration beginning at four weeks off dox. By end stage, rNLS8 mice had significantly smaller brains than non-Tg littermates.

Observed

rNLS8 lost motor neurons in the lumbar spinal cord by six weeks off dox.

Observed

Cytoplasmic inclusions of TDP-43 occur as early as one week off dox in neurons in the brain. Inclusions accumulate over time and are present in many brain regions, including the motor cortex. TDP-43 inclusions are relatively rare in the spinal cord. Ubiquitin-positive inclusions are also seen.

Observed

Astrogliosis develops in many brain regions, including layer V of the motor cortex.

Observed

Denervation of the hindlimb muscle tibialis anterior was detectable by four weeks off dox, that is, two weeks prior to detectable loss of lower motor neurons.

rNLS8 mice develop a variety of motor impairments, starting with a deficit in hindlimb clasping and a fine tremor in the forelimb and/or hindlimb. They also develop progressive loss of grip strength (as measured by the wire-hang test) and a progressive decline in coordinated movement and balance (as measured by the accelerating Rotarod).

Observed

Body mass peaked at approximately 7 weeks of age (i.e., two weeks off dox) and then progressively dropped. Excessive loss of body weight (>30% decrease from peak weight) often defined end-stage.

Observed

rNLS8 mice die prematurely. They reach end-stage 8-18 weeks off dox, with a median survival of 10.3 weeks off dox.

Despite high levels of cytoplasmic FUS, neuronal inclusions were not observed.

No Data

No data.

Observed

A number of abnormalities were detected in the hindlimb musculature by electromyography (EMG). These phenotypes were detectable by 8-12 months of age and included fibrillation potentials, muscle denervation, and a reduction in the number of motor units.

No Data

No data.

Absent

Not observed.

No Data

No data.

Observed

Hemizygous mice sporadically developed intestinal swelling leading to premature death (mean survival 118 days). Homozygous mice were more severely affected (50 percent of the original cohort died around 59 days of age).

Upper motor neuron loss was not observed, although vacuolization occurred in brainstem neurons.

Observed

Motor neurons in the spinal cord and brainstem degenerated with overt neuronal loss in the ventral horn in some regions of the spinal cord by 19 weeks. The degenerative process involved extensive vacuolization.

Absent

Not observed.

Observed

Astrogliosis occurs in the spinal cord by 11 weeks of age, becoming more severe with age.

Although outright upper motor neuron loss is absent or rare, degenerative signs (e.g., swollen neurites, Gallyas-positive aggregates, vacuoles, and neuritic spheroids) have been shown in motor regions of the cerebral cortex by five months of age.

Observed

Up to 50% loss of motor neurons in the cervical and lumbar segments of the spinal cord at end stage.

Observed

Inclusions accumulate in spinal motor neurons starting around 82 days of age. Inclusions generally take the form of spheroids or Lewy-body-like inclusions and commonly include a variety of neuronal intermediate filament proteins. TDP-43-positive inclusions are not present.

Observed

Gliosis, including the proliferation of reactive microglia and astrocytes, develops in parallel with motor neuron degeneration in the spinal cord.

These mice lose corticospinal tract axons, but outright loss of cortical neurons has not been reported in the model. When crossed with a Thy-1YFP model to label layer 5 pyramidal neurons, mice expressing TDP-43 (A315T) had fewer neurons at 15 weeks of age than YFP littermate controls (Zhang et al., 2016).

Absent

Most studies reported no lower motor neuron loss. One study observed 20% loss of large ventral horn neurons, possibly dependent on diet and how long the mice live in an individual colony.

Observed

Ubiquitinated inclusions in the cytoplasm of spinal motor neurons and cortical layer V neurons. No evidence for cytoplasmic TDP-43 inclusions.

Observed

Reports of astrocytosis in cortical layer 5 and in the spinal cord, as well as microgliosis in the spinal cord.

Observed

Denervation of neuromuscular junctions at end stage (~11% on normal diet; ~20% loss on a gel diet).

Observed

Atrophy of gastrocnemius muscle (gel diet).

Observed

Deficits have been reported in nonspecific measures of strength and coordination such as the Rotarod (males and females) and hanging-wire test (males). A severely impaired gait (“swimming gait”) was observed in mice fed a gel diet.

Survival is limited by severe gastrointestinal dysfunction and can be prolonged with a gel diet. Lifespan varies, but in general on a standard diet males live about 3 months and females about 6 months.

Cytoplasmic accumulation of TDP-43 was observed by 10 months of age in the spinal cord. Furthermore, cytoplasmic aggregates were observed and often co-localized with ubiquitin. These inclusions are not detected at three months of age.

Observed

Progressive gliosis of both astrocytes and microglia, starting at a young age (by 3 months) in the brain and spinal cord.

No Data

Unknown.

No Data

Unknown.

Observed

At 38 weeks of age, mice develop impairments on the accelerating Rotarod relative to non-Tg littermates.

Ubiquitin-positive cytoplasmic inclusions in neurons of the ventral horn and brainstem. Cytoplasmic aggregates of TDP-43 are largely absent, although rare phospho-TDP-43 inclusions were observed, especially at end-stage.

Observed

Mice exhibiting muscle weakness had astrocytosis in the ventral horn of the spinal cord.

No Data

Unknown.

Observed

Atrophy of muscle fibers in the quadriceps muscle of weak mice observed by day 44.

Observed

Progressive motor impairment, characterized by weakness, a decline in grip strength, and reduction in stride length. Weakness was usually more pronounced in the hindlimbs.

Observed

Progressive weight loss.

Observed

Line 23 mice survived about 2.5 months, mean survival 75 days. It was not reported whether this survival analysis includes males, females or both. Colony at Jackson Labs has longer mean survival.

Cytoplasmic accumulation of TDP-43 was observed by 10 months in the spinal cord. Cytoplasmic aggregates occurred and often co-localized with ubiquitin. These inclusions are not detected at 3 months of age.

Observed

Progressive gliosis of both astrocytes and microglia, starting at a young age (by 3 months) in the brain and spinal cord.

Observed

In 10-month-old mice, approximately 10% of NMJs in the gastrocnemius muscle were denervated, with another 20% partially denervated.

No Data

Unknown.

Observed

Performance on the Rotarod was comparable to non-Tg littermates until 36 weeks of age, and became progressively worse with age.

Severe neuronal loss in all CA regions of the hippocampus of homozygous mice. Neuronal loss was also observed in layer V cortical neurons and thalamic neurons.

Observed

Neuronal loss was observed in the spinal cords of homozygous mice.

Observed

Some homozygous mice developed cytoplasmic inclusions in layer V cortical neurons. These were often, but not always, ubiquitin–positive. They were not universally observed, even in end-stage mice.

Observed

Elevated astrogliosis and microgliosis compared with non-Tg controls, especially in the motor cortex and spinal cord. Gliosis in the hippocampus was seen at end stage.

No Data

Unknown.

No Data

Unknown.

Observed

Motor impairment developed quickly, by 11 days of age in homozygous mice, starting with an abnormal clasping reflex. They also develop a hunched posture, muscle twitches, and reduced mobility. Paralysis developed within days, leading to death. Hemizygotes do not develop motor symptoms until about one year of age, and impairment varied from mouse to mouse.

Observed

Early postnatal growth retardation in homozygous mice. By day 17 their average body weight is about half that of non-Tg controls.

Observed

Homozygous mice survived an average of just 17 days. In contrast, hemizygous Mt-TAR6 mice lived up to 24 months (average survival ~16.4 months).

In homozygous mice, quantitative loss of neurons occurs in the motor cortex compared with non-Tg littermates. Both superficial and deep cortical layers of the anterior cortex are affected.

Observed

By day 18, homozygous mice exhibited about 25 percent loss of motor neurons in the lumbar spinal cord compared with non-Tg littermates.

Observed

Homozygous mice developed cytoplasmic inclusions in the brain and spinal cord, many of which were ubiquitin-positive. A minority of inclusions co-labeled with TDP-43. Ultrastructural analysis revealed ubiquitin–negative cytoplasmic inclusions in anterior horn neurons to be abnormal accumulations of mitochondria.

Observed

Astrogliosis and microgliois especially in cortical layer V of the anterior cortex, including motor and somatosensory cortex, and in the spinal cord.

No Data

No data.

No Data

No data.

Observed

Homozygous mice exhibit an abnormal clasping reflex by postnatal day 14. Other early motor deficits include a shortened stride, a wide stance, and frequent stumbling. By day 18, reduced performance on the Rotarod. Complete paralysis occurs ~10 days after onset.